Domain topology, stability, and translation speed determine mechanical force generation on the ribosome
The concomitant folding of a nascent protein domain with its synthesis can generate mechanical forces that act on the ribosome and alter translation speed. Such changes in speed can affect the structure and function of the newly synthesized protein as well as cellular phenotype. The domain propertie...
| Main Authors: | , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
National Academy of Sciences
2019
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| _version_ | 1797055039819218944 |
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| author | Leininger, SE Trovato, F Nissley, DA Edward P O'Brien |
| author_facet | Leininger, SE Trovato, F Nissley, DA Edward P O'Brien |
| author_sort | Leininger, SE |
| collection | OXFORD |
| description | The concomitant folding of a nascent protein domain with its synthesis can generate mechanical forces that act on the ribosome and alter translation speed. Such changes in speed can affect the structure and function of the newly synthesized protein as well as cellular phenotype. The domain properties that govern force generation have yet to be identified and understood, and the influence of translation speed is unknown because all reported measurements have been carried out on arrested ribosomes. Here, using coarse-grained molecular simulations and statistical mechanical modeling of protein synthesis, we demonstrate that force generation is determined by a domain’s stability and topology, as well as translation speed. The statistical mechanical models we create predict how force profiles depend on these properties. These results indicate that force measurements on arrested ribosomes will not always accurately reflect what happens in a cell, especially for slow-folding domains, and suggest the possibility that certain domain properties may be enriched or depleted across the structural proteome of organisms through evolutionary selection pressures to modulate protein synthesis speed and posttranslational protein behavior. |
| first_indexed | 2024-03-06T19:05:51Z |
| format | Journal article |
| id | oxford-uuid:151bb201-433d-49ea-a2f6-b1d6ce8db645 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:05:51Z |
| publishDate | 2019 |
| publisher | National Academy of Sciences |
| record_format | dspace |
| spelling | oxford-uuid:151bb201-433d-49ea-a2f6-b1d6ce8db6452022-03-26T10:23:37ZDomain topology, stability, and translation speed determine mechanical force generation on the ribosomeJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:151bb201-433d-49ea-a2f6-b1d6ce8db645EnglishSymplectic ElementsNational Academy of Sciences2019Leininger, SETrovato, FNissley, DAEdward P O'BrienThe concomitant folding of a nascent protein domain with its synthesis can generate mechanical forces that act on the ribosome and alter translation speed. Such changes in speed can affect the structure and function of the newly synthesized protein as well as cellular phenotype. The domain properties that govern force generation have yet to be identified and understood, and the influence of translation speed is unknown because all reported measurements have been carried out on arrested ribosomes. Here, using coarse-grained molecular simulations and statistical mechanical modeling of protein synthesis, we demonstrate that force generation is determined by a domain’s stability and topology, as well as translation speed. The statistical mechanical models we create predict how force profiles depend on these properties. These results indicate that force measurements on arrested ribosomes will not always accurately reflect what happens in a cell, especially for slow-folding domains, and suggest the possibility that certain domain properties may be enriched or depleted across the structural proteome of organisms through evolutionary selection pressures to modulate protein synthesis speed and posttranslational protein behavior. |
| spellingShingle | Leininger, SE Trovato, F Nissley, DA Edward P O'Brien Domain topology, stability, and translation speed determine mechanical force generation on the ribosome |
| title | Domain topology, stability, and translation speed determine mechanical force generation on the ribosome |
| title_full | Domain topology, stability, and translation speed determine mechanical force generation on the ribosome |
| title_fullStr | Domain topology, stability, and translation speed determine mechanical force generation on the ribosome |
| title_full_unstemmed | Domain topology, stability, and translation speed determine mechanical force generation on the ribosome |
| title_short | Domain topology, stability, and translation speed determine mechanical force generation on the ribosome |
| title_sort | domain topology stability and translation speed determine mechanical force generation on the ribosome |
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